The present invention concerns devices for picking up and metering sample liquids and analytical test systems for determining analytes in a sample liquid which, in addition to such devices for picking up and metering sample liquids, have a reaction cuvette for carrying out the reactions necessary to determine the analyte.
In addition, the invention concerns the use of such analytical test systems for determining analytes in a sample liquid and methods for determining analytes in a sample liquid in which such analytical test systems are used.
The present invention is in the field of sampling and sample metering and performing analytical tests to determine an analyte in a sample liquid. In particular, it concerns analytical test devices and methods which are suitable for detection methods that employ liquid reagents or buffers or which comprise a plurality of consecutive individual steps and reactions.
The determination of analytes in a sample liquid is of major importance in many industrial and scientific fields for example for analytical investigations of the environment and foods and also for medical and diagnostic examinations so that numerous analytical methods and test devices have been developed in the past. Many methods of determination require a plurality of consecutive analytical reactions with a variety of reagents and reaction conditions which have to be carried out successively in the form of process steps according to a fixed protocol. Usually a large number of manual process steps such as pipetting, mixing, transfer into other reactions spaces, incubation phases or centrifugation or separation steps are necessary to carry out such analytical methods which are often prone to errors and thus can lead to falsified analyte determinations. Although different test systems have been developed in the past in which it has been attempted to simplify and automate such process steps, such test systems are often still complex and thus expensive to manufacture. Furthermore, they usually require specially trained operating personnel and/or complicated and expensive laboratory equipment to carry out the analyte determination. Although it is often possible to automate a large number of process steps in such systems, the steps of sample collection, sample preparation and/or of the metered introduction of sample into the system usually still have to be carried out manually and are thus prone to errors.
Recently microfluidic test systems have been used to try to transport the applied sample through specially designed channels and chambers so that it comes into contact there with the detection reagents at defined sites. In this process the sample liquid or the reaction mixture successively passes through a plurality of reaction, incubation and/or detection areas thus enabling a sequence of spatially and/or chronologically separated reaction steps. However, this requires devices that are very complicated to manufacture and thus expensive, and often also requires additional process steps such as dilution or mixing steps which usually have to be carried out outside of the device because such microfluidic devices can often only be equipped with dry chemistry reagents for manufacturing and stability reasons. In such microfluidic devices liquids are usually transported by means of capillary forces which in turn makes high demands on the accuracy and form of the capillary channels and consequently results in correspondingly expensive and complex manufacturing processes. Liquid transport by externally applied forces such as by centrifugation, rotation or also by pumps is usually less demanding on the test device itself but these technologies require additional costly apparatuses such as centrifuges or pumps.
Another group of analytical test elements are carrier-bound tests such as test carriers or test strips based on dry chemistry. In this case the reagents and in particular specific detection reagents and auxiliary reagents are embedded or immobilized in appropriate detection elements of a solid carrier. In the classical test strip formats all reagents are present as dry chemicals on the test strips and the reagents are only dissolved by the sample liquid and thus brought into a reactive state. However, since not all reagents are suitable for stable storage in a dry chemistry form, the application of such dry chemistry test strips is limited to detection reactions in which all reaction partners can be stored in a dry chemistry form. Also in the case of carrier-bound tests, the sample is usually applied manually by pipetting a certain sample volume or contact with a large unmetered volume of the sample liquid such as a drop of blood of undefined size. Dilution steps that may be necessary also have to be carried out manually before sample application in most test strip formats. Attempts at also storing liquid reagents on test strips also increases the complexity of their superstructural parts and thus led to less user-friendly and also more expensive test systems.
The sample pick up devices and analytical test systems described in the prior art are characterized by a complex design or a limitation to dry chemistry reagents. The manufacture and assembly of such complex test elements are, however, usually very complicated and costly. In some cases additional complex instruments are required to carry out the analyte determinations such as to centrifuge or rotate the test elements which increases the complexity of the entire analytical system and its purchase costs and thus also increases the cost per test carried out.
No devices are known from the prior art for picking up and metering sample liquids and no analytical test systems are known for determining analytes in a sample liquid which can be manufactured in the simplest possible and most cost-effective manner, operated in as simple and less error-prone manner as possible, are not limited to the use of dry chemistry reagents and which enable an exact metering and/or dilution of the sample liquid to be examined with buffer or diluent solutions or reagent solutions.